Wiskott-Aldrich Syndrome Protein

The protein of Wiskott – Aldrich Syndrome ( The Wiskott – Aldrich Syndrome Protein, WASp ) consists of 502 amino acid residues ^[1] and has a complex domain structure. It is expressed in hematopoietic cells and plays an important role in the reorganization of the cytoskeleton , signal transduction, and apoptosis ^[2] .

Wiscott — Aldrich Syndrome
PDB rendering based on 1cee.
Available structures PDB Ortholog Search: PDBe , RCSB PDB ID List , , , , ,
Identifiers
Symbol	; IMD2; SCNX; THC; THC1; Wasp
External id	GeneCards :
Gene ontology Function • • • • Cell component • • • Biological process • • • • • • • • • • • • • Sources: Amigo / QuickGO
RNA expression profile
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RefSeq (protein)
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The WAS gene, mutations in which lead to the development of Wiskott-Aldrich syndrome , is located on the short arm of the X chromosome in the region of Xp11.4 - Xp11.21. More precisely, the WAS gene is located from48,683,789 to the 48,691,426th base pair on the X chromosome ^[3] . Mapping of the gene was carried out in 1994, it was found that the WAS gene consists of 12 exons and 11 introns ^[4] with a total length of approximately 1800 pairs of nucleotides ^{[5] [6]} .

At the C-terminus of the WASp protein, in the immediate vicinity of one another, the binding domains of monomeric actin and the Agr2 / 3 complex are located. This provides a spatial convergence of these molecules and facilitates the actin polymerization. At the N-terminus and in the central part of the protein, there are various regulatory domains (WH1, GBD, Polu-Pro site), which provide interconnection with many special protein molecules and phospholipids of the membranes. Thus, the WASp protein can serve as a mediator in the interaction of various specific factors with membrane structures and participate in the actin polymerization ^{[7] [8]} .

The occurrence of a mutation in the gene responsible for the synthesis of WASp protein leads to the appearance of a defective form of the protein or its complete absence, which entails the development of impaired immunity and hemostasis. At least 350 mutations are known ^[3] in the WAS gene, which are responsible for the development of X-linked Wiskott-Aldrich syndrome. Their main number falls on nucleotide substitutions (missense / nonsense mutations), splicing mutations and small deletions. Small insertions and large deletions are also detected ^[9] .

In patients with missense mutations , as a rule, there is a mild course of the disease, manifested mainly by thrombocytopenia. Patients with various deletions, nucleotide insertions, nonsense mutations, and splicing site mutations are characterized by more severe clinical manifestations ^{[10] [11]} .